Isotypes in Human Immunoglobulin λ-Chains

Hess, M; Hilschmann, Norbert; Rivat, L; Rivat, C.; Ropartz, C

doi:10.1038/newbio234058a0

Cited by 47 publications

(14 citation statements)

References 32 publications

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“…Protein NEI has an arginine a t position 190 and a serine a t position 154, so it can be classified as Oz-Kern-. Both of these interchanges define a recent gene duplication and subsequent mutations, since all normal individuals apparently carry all Oz-, Oz+, Kern-and Kern+ copies [46,47].…”

Section: The Constant Partmentioning

confidence: 99%

The Primary Structure of a Monoclonal Human λ‐Type Immunoglobulin L‐Chain of Subgroup II (Bence‐Jones Protein NEI)

Garver

Hilschmann

1972

European Journal of Biochemistry

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Protein NEI, which has a molecular weight of 23500 and contains 216 amino acids, was isolated from the urine of a patient with multiple myeloma by salt-precipitation and purified by ion-exchange chromatography, block electrophoresis and gel filtration. 23 tryptic peptides have been isolated from the aminoethylated protein and 13 chymotryptic peptides from the carboxymethylated protein by ion-exchange chromatography. Sequence studies have mainly been carried out with the tryptic peptides ; the chymotryptic peptides have been used for overlaps in the variable region, since the alignment of the tryptic peptides by homology was not unambiguous.Protein NEI belongs to subgroup I1 of the A-chains. It has a series of subgroup specific exchanges and a subgroup specific deletion a t position 96. Protein NEI differs from all other A-chains of subgroup I1 by possessing a sixth cysteine residue. This additional cysteine residue a t position 88 is so far unique, as it is adjacent to an invariant cysteine a t position 87. Protein NEI also contains a carbohydrate moiety attached to an aspartic acid or asparagine (Asx) residue a t position 93, one of the hypermutable areas of the variable part. Furthermore we conclude by comparison with other A-chains that all completely elucidated A-chains can be ordered into four subgroups. The subgroups and linkage groups within subgroups are in complete agreement with an evolutionary origin of antibody variability and are incompatible with somatic hypermutation models.Structural studies with monoclonal immunoglobulins have provided the first insight into the genetic mechanism of antibody formation [l--51. Since the molecule is divided into a variable and a constant part, the genetic control of the immunoglobulins is more complicated than with other protein families.There is, however, an increasing amount of evidence, that the extreme heterogeneity of the variable parts, which is responsible for the specificity of the antibody, is genetically determined. Crucial in this respect is the high order of regularity which governs the amino acid exchanges and deletions of the variable parts. These linked amino acid exchanges (subgroup and subsubgroups) can only be explained by an evolutionary process [3,6--81.One of the proteins which has contributed to the understanding of this variability is Bence-Jones protein NEI, a A-type L-chain of subgroup 11. The primary structure of this protein has been reported previously in a short communication

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Section: The Constant Partmentioning

confidence: 99%

The Primary Structure of a Monoclonal Human λ‐Type Immunoglobulin L‐Chain of Subgroup II (Bence‐Jones Protein NEI)

Garver

Hilschmann

1972

European Journal of Biochemistry

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“…These differences are likely to be due to a genetic polymorphism, rather than to minor isotypic variations analogous to the human Kern, Oz. and Mcg markers (39)(40)(41). Accordingly, hybridization of the chicken genomic DNA with our CA probe reveals only one gene under nonstringent conditions (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Complete sequence of a chicken lambda light chain immunoglobulin derived from the nucleotide sequence of its mRNA.

Reynaud¹,

Dahan²,

Weill³

1983

Proc. Natl. Acad. Sci. U.S.A.

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Recombinant cDNA plasmids have been constructed from chicken spleen poly(A)-containing RNA. Two clones have been selected and provide the sequence determination of a chicken A immunoglobulin light chain: they include the complete variable, constant, and 3' untranslated regions of the chicken A light chain mRNA and part of the leader sequence. Comparison of the chicken light chain constant region with both human and mouse A constant sequences indicates 61% homology at the amino acid level. Unexpectedly, the chicken variable sequence is 53-63% homologous to human variable sequences when it is compared to the various A subgroups and only 42% homologous to the mouse VA1 sequence. The degree of homology between the variable regions of these three species does not so easily correlate with their phylogenetic relationship. Fowls offer a privileged model for studying B cell ontogeny, for they possess a primary organ of B cell differentiation, the bursa of Fabricius, which has no mammalian equivalent. In the chicken embryo, a wave of colonization of the bursa by stem cells of intraembryonic origin arises on the 8th day of development (6). From the 11th to the 14th day, la differentiation antigen and then surface immunoglobulin are progressively expressed by the progeny of these cells, until day 20, when 90% of bursal cells are surface-IgM-positive (7). Chicken B lymphocyte precursors can thus be isolated from this organ independently of the acquisition of any distinctive pre-B cell marker. They constitute a unique dynamic model for studying cellular interactions and enzymatic factors involved in the reorganization of immunoglobulin genes during the initial commitment of stem cells to the B lineage.

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“…Based on chemical and serological analyses, X chains bearing the Mcg, Kern, or Oz isotypic markers are relatively uncommon, accounting for only 11%, 18%, and 25%, respectively, of the total X light chain population of a normal individual (6,7,15,26,27 (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

“…Three different isotypic variants, designated Oz (5), Kern (6), and Mcg (7), are characterized by site-specific sequence substitutions and the CA genes encoding these sequences have been identified (2). In addition, 10 other sequence variations in CA have been recognized among monoclonal light chains (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), but the genetic basis for these differences is not known.…”

mentioning

confidence: 99%

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

Frangione¹,

Moloshok²,

Prelli³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Serologic, structural, and genetic analyses have shown that the constant (C) region of human Kc light chains is encoded by a single gene, whereas that of K chains is encoded by multiple genes. We have determined the complete C region amino acid sequence of two (J), and constant (C), widely separated in germ-line DNA. The V gene encodes the first 95-100 residues of the VL, and the J gene encodes the remaining 13 residues. In the course of B-cell development, gene segments V and J are joined together and eventually linked to the CL-encoding gene segment C. Despite these similarities, the chromosomal location, number, and order of K and X chain-encoding gene segments are strikingly different. Human K chains, for example, are the products of tandemly arranged V, J, and C gene segments located on chromosome 2 (1). During somatic differentiation, one each of multiple germ-line VK and JK genes is joined together; the selected V/J gene is eventually spliced to a single CK gene (1). In contrast, the V, J, and C genes encoding X chains are located on chromosome 22 and differ from their K counterparts by the presence of at least six CA genes (2); furthermore, the CA genes are in tandem and, in the mouse (3), are each preceded by a J gene segment.Polymorphism among human CA genes was first evidenced through serological and sequence analyses of monoclonal A light chains and, more recently, has been demonstrated at the genomic level (2, 4). Three different isotypic variants, designated Oz (5), Kern (6), and Mcg (7), are characterized by site-specific sequence substitutions and the CA genes encoding these sequences have been identified (2). In addition, 10 other sequence variations in CA have been recognized among monoclonal light chains (8-18), but the genetic basis for these differences is not known.In the course of determining the complete amino acid sequence of two monoclonal human XVI amyloid-associated MATERIALS AND METHODSProtein Isolation and Purification. Bence Jones proteins Mor and Sut were isolated from urine specimens by zone electrophoresis on polyvinyl chloride blocks (Pevikon; Kemanord, Sweden) and were further purified by gel filtration through agarose/polyacrylamide gel columns (Ultrogel AcA54, LKB) as described (20). The purity and molecular weights of the proteins were determined by NaDodSO4/ polyacrylamide gel electrophoresis with or without 0.1 M 2-mercaptoethanol (21) and by immunoelectrophoresis using antisera to light chain and normal human sera.Complete Reduction and Radioalkylation. Proteins Mor and Sut were reduced in 6 M guanidine/0.6 M Tris HCl/1 mM EDTA, pH 8.2, containing 5 mM dithiothreitol for 1 hr at 370C and were alkylated by the addition of iodo[14C]acetic acid (0.7 mCi/mmol; 1 Ci = 37 GBq; Amersham) to a final concentration of 11 mM (22). After incubation for 1 hr at 23°C, the samples were desalted by passage through Sephadex G25 fine (Pharmacia) columns equilibrated in 1 M acetic acid and then lyophilized.Peptide Preparation. Trypsin and staphylococcal protease V8 (23) were us...

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Isotypes in Human Immunoglobulin λ-Chains

Cited by 47 publications

References 32 publications

The Primary Structure of a Monoclonal Human λ‐Type Immunoglobulin L‐Chain of Subgroup II (Bence‐Jones Protein NEI)

The Primary Structure of a Monoclonal Human λ‐Type Immunoglobulin L‐Chain of Subgroup II (Bence‐Jones Protein NEI)

Complete sequence of a chicken lambda light chain immunoglobulin derived from the nucleotide sequence of its mRNA.

Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

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